Someone in the world is newly infected with tuberculosis (TB) bacilli every second. Overall one-third of the world's population is currently infected with tuberculosis and it has been estimated that 5-10% of those people are expected to become sick or infectious at some point in their lifetime. The major challenges for tuberculosis control are the development of multidrug-resistant tuberculosis (MDR-TB) strains and the increasing numbers of immunocompromised individuals with HIV infections who are highly susceptible to the disease. No new effective treatments have been developed since the introduction of Rifampicin in 1971, even though there have been significant advances in drug development technologies. Consequently there is an urgent need to develop new, potent, fast-acting anti-tubercular drugs with low-toxicity profiles that can be used in conjunction with drugs used to treat HIV infections.
As a part of investigation of new chemotherapeutic agents from this laboratory, over the past eight years our research efforts have been focused towards the intervention of new scaffolds with good anti-mycobacterial activity and eventually to develop new anti-tubercular agents that can improve the current therapeutic regimen as well as effective in the treatment of MDR-TB (Kamal, A.; Babu, A. H.; Ramana, A. V.; Sinha, R.; Yadav, J. S.; Arora, S. K. Bioorg. Med. Chem. Lett. 2005, 15, 1923-1926.; Kamal, A.; Reddy, K. S.; Ahmed, S. K.; Khan, M. N. A.; Sinha, R. K.; Yadav, J. S.; Arora, S. K. Bioorg. Med Chem. 2006, 14, 650-658.; Kamal, A.; Ahmed, S. K.; Reddy, K. S.; Khan, M. N. A.; Shetti, R. V. C. R. N. C.; Siddhardha, B.; Murthy, U. S. N.; Khan, I. A.; Kumar, M.; Sharma, S.; Ram, A. B. Bioorg. Med. Chem. Lett. 2007, 17, 5419-5422; Kamal, A.; Azeeza, S.; Malik, M. S.; Faazil, S. Int. J. of Medical and Biological Frontiers 2010, 16, 535-568.; Kamal, A.; Shetti, R. V. C. R. N. C.; Azeeza, S.; Ahmed, S. K.; Swapna, P.; Malla Reddy, A.; Khan, I. A.; Sharma, S.; Abdullah, S. T.; Eur. J. of Med. Chem. 2010, 45, 4545-4553).
Nitrofuranylamides compounds (11(a-c)) that have been discovered recently and showed potent anti-tuberculosis activity (Huedle, J. G.; Budha, N. R.; Carson, E. I.; Qi, J.; Scherman, M. S.; Cho, S. H.; McNeil, M. R.; Lenaerts, A. J.; Franzblau, S. G.; Meibohm, B.; Lee, R. E. J. Antimicro. Chemother. 2008, 62 1037-1045). Nitrofuranyl amide compounds exhibited good thearapeutic value. They are members of an emerging new class of nitroaromatic antibiotics that are currently being intensively investigated as new anti-tuberculosis drugs. (Tangallapally, R. P.; Yendapally, R; Lee, E. R.; Lenaerts, A. J. M.; and Lee, R. E. J. Med. Chem., 2005, 48, 8261-8269); Tangallapally, R, P.; Yendapally, R.; Lee, R. E.; Hevener, K.; Jones, V. C.; Lenaerts, A. J. M.; McNeil, M. R.; Wang, Y.; Franzblau, S.; Lee, R. E. J. Med. Chem., 2004, 47, 5276-5283).
Oxadiazalone (12(ac)) are a class of compounds comprising anti-tubercular activity and they showed interesting activity (Mamolo, M. G.; Zampieri, D.; Vio, L.; Fermeglia, m.; Ferrone, M.; Pricl, S; Scialino, G. and Banfi, E. Bioorg. Med. Chem., 2005, 13, 3797-3809).
FIG. 1 represents structural formula of the compounds: N2-(3-fluorophenyl)-5-nitro-2-furamide (11a), N2-(4-pyridyl)-5-nitro-2-furamide (11b), N2-[4-(4-benzylpiperidino)phenyl]-5-nitro-2-furamide (11c), 3-[(3-methylpiperidino)methyl]-5-(4-pyridyl)-2,3-dihydro-1,3,4-oxadiazol-2-one (12a), 3-[(4-methylpiperazino)methyl]-5-(4-pyridyl)-2,3-dihydro-1,3,4-oxadiazol-2-one (12b), 3-[(4-benzylpiperidino)methyl]-5-(4-pyridyl)-2,3-dihydro-1,3,4-oxadiazol-2-one (12c).

FIG. 1
Keeping this aspect in mind, nitrofurfuryl substituted phenyl linked piperidino-oxadiazolone compounds were designed and synthesized.